KRÜPPEL-LIKE FACTOR 9 ENHANCES THYROID HORMONE RECEPTOR β AUTOINDUCTION IN TADPOLE BRAIN IN VIVO, INCREASING TISSUE SENSITIVITY TO THYROID HORMONE AND ACCELERATING METAMORPHOSIS

Abstract

Event Abstract Back to Event KRÜPPEL-LIKE FACTOR 9 ENHANCES THYROID HORMONE RECEPTOR β AUTOINDUCTION IN TADPOLE BRAIN IN VIVO, INCREASING TISSUE SENSITIVITY TO THYROID HORMONE AND ACCELERATING METAMORPHOSIS Fang Hu1, Joseph Knoedler1 and Robert J. Denver1* 1 University of Michigan, Molecular, Cellular and Developmental Biology, United States Thyroid hormone (T3) receptor β (TRβ) is a direct T3 target gene that is strongly induced (autoinduced) during tadpole metamorphosis. TRβ autoinduction is thought to be critical for hormone action during metamorphosis. The transcription factor Krüppel-like factor 9 (KLF9) is the most rapidly responding T3 target gene thus far identified. Previously, we showed in the Xenopus cell line XTC-2 that KLF9 associates with the TRβ promoter to accelerate and enhance TRβ autoinduction. Here we show that KLF9 promotes TRβ autoinduction in tadpole brain in vivo. We used electroporation-mediated (EM) gene transfer to transfect plasmids into the brains of early prometamorphic tadpoles to express wild type or mutant forms of KLF9. Forced expression of KLF9 increased basal TRβ mRNA expression in euthyroid tadpoles, but had no effect in methimazole-treated, hypothyroid animals, suggesting that KLF9’s major action is to enhance liganded TR action. Similar to our findings in XTC-2 cells, forced expression of KLF9 accelerated TRβ autoinduction in tadpole brain in vivo and enhanced T3-dependent induction of the TR target gene TH/bZip. Consistent with our previous mutagenesis experiments conducted in XTC-2 cells, the actions of KLF9 in vivo did not depend on its DNA binding activity, but required the second transactivation domain ‘B’. Chronic, forced expression of KLF9 in tadpole brain accelerated metamorphosis, which we hypothesize is due to KLF9 increasing TRβ expression, and thereby enhancing tissue sensitivity to T3. In support of this hypothesis, we found that forced expression of TRβ in tadpole brain in vivo by EM gene transfer increased expression of TR target genes. We conclude that the immediate early transcription factor KLF9 participates in a transcriptional regulatory network to promote TRβ autoinduction in vivo, forming a positive feedback loop that sensitizes the cell to further hormonal stimulation owing to the production of more TRβ. Acknowledgements Supported by NIH grant R01 NS046690 and NSF grant IOS 0922583 to RJD Keywords: Autoinduction, Hypothalamus, metamorphosis, nuclear receptor, Thyroid hormone, Xenopus Conference: NASCE 2011: The inaugural meeting of the North American Society for Comparative Endocrinology, Ann Arbor, United States, 13 Jul - 16 Jul, 2011. Presentation Type: Poster Topic: Nuclear receptors Citation: Hu F, Knoedler J and Denver RJ (2011). KRÜPPEL-LIKE FACTOR 9 ENHANCES THYROID HORMONE RECEPTOR β AUTOINDUCTION IN TADPOLE BRAIN IN VIVO, INCREASING TISSUE SENSITIVITY TO THYROID HORMONE AND ACCELERATING METAMORPHOSIS. Front. Endocrinol. Conference Abstract: NASCE 2011: The inaugural meeting of the North American Society for Comparative Endocrinology. doi: 10.3389/conf.fendo.2011.04.00019 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 18 Jul 2011; Published Online: 09 Aug 2011. * Correspondence: Prof. Robert J Denver, University of Michigan, Molecular, Cellular and Developmental Biology, Ann Arbor, United States, Rdenver@umich.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Fang Hu Joseph Knoedler Robert J Denver Google Fang Hu Joseph Knoedler Robert J Denver Google Scholar Fang Hu Joseph Knoedler Robert J Denver PubMed Fang Hu Joseph Knoedler Robert J Denver Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.